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DMD — Jen-Chywan Wang, Ph.D.

Wang and colleagues are exploring the possibilities of targeting the unwanted side effects that come with glucocorticoid treatment, while preserving the drugs' anti-inflammatory activity.

Duchenne Muscular Dystrophy (DMD)

MDA has awarded a research grant totaling $220,000 over two years to Jen-Chywan Wang, assistant professor at the University of California, Berkeley. The new funds will help support Wang’s study of the effects of chronic glucocorticoid (steroid) treatment in Duchenne muscular dystrophy (DMD).

Glucocorticoids are potent anti-inflammatory agents that frequently are used to delay and relieve DMD symptoms, including rapid progression of muscle degeneration, loss of ambulation, paralysis and shortened lifespan. Although the drugs are beneficial, they cause unwanted side effects, one of which is loss of muscle mass.

In their new work, Wang and colleagues plan to first investigate the means by which glucocorticoids cause muscles to degenerate. The investigators previously identified two genes that have been linked to reduced muscle mass; now they plan to examine how glucocorticoids increase those genes' activity ("expression").

The team also plans to identify chemical compounds that specifically suppress the ability of glucocorticoids to activate the two suspect genes without affecting the drugs' anti-inflammatory activity. In research models of the disease, Wang's team will test whether such chemical compounds can reduce inflammation without causing muscle loss.

Additionally, the investigators have identified another eight genes that exert control over the total amount of protein in cells. The group will test whether increasing the expression of these genes leads to muscle loss, and whether the genes are responsible for glucocorticoid-induced muscle loss. Such genes could potentially be targeted in an effort to improve the effectiveness of glucocorticoid treatment in DMD.Wang’s work could lead to improved glucocorticoid-based therapies for individuals with DMD.

"Private agencies such as MDA play a vital role in sustaining specific interest in particular diseases," Wang said. "This support from MDA will provide a tremendous boost to our research in the understanding of how steroid hormones affect skeletal muscle biology."